Preoperative Occult Neurodegeneration and Postoperative Delirium

术前隐匿性神经变性和术后谵妄

• 批准号: 10589054
• 负责人: GREGORY CROSBY
• 金额: $ 89.09万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589054
• 关键词: Acceleration; Acute; Address; Age; Age Years; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloidosis; Anesthesia procedures; Biological Markers; Brain; CD14 gene; Cerebrum; Characteristics; Clinical; Cognition; Cognitive; Confusion; Data; Delirium; Dementia; Development; Diagnosis; Distress; Elderly; Future; Glial Fibrillary Acidic Protein; Immune response; Impaired cognition; Impairment; Inflammation; Inflammatory Response; Injury; Lead; Light; Magnetic Resonance Imaging; Measures; Morbidity - disease rate; Nerve Degeneration; Neurobehavioral Manifestations; Neurobiology; Neurodegenerative Disorders; Neuropathogenesis; Observational Study; Operative Surgical Procedures; Outcome; Pathogenicity; Pathology; Patients; Perioperative Care; Plan B; Plasma; Positron-Emission Tomography; Postoperative Period; Predisposition; Prevalence; Principal Investigator; Procedures; Proteome; Proxy; Recovery of Function; Research; Risk Assessment; Risk Factors; Severities; Spinal Puncture; Spine surgery; Surgical complication; Symptoms; Syndrome; Tauopathies; Testing; Time; UCHL1 gene; Validation; Work; axon injury; blood-based biomarker; brain magnetic resonance imaging; cerebral atrophy; cost; human old age (65+); improved; improved outcome; innovation; monocyte; nerve injury; neural; neurofilament; neuroinflammation; neuropathology; novel; older patient; postoperative delirium; primary outcome; programs; prospective; risk prediction; secondary outcome; surgical risk; systemic inflammatory response; tau Proteins; transcriptome

Program Director/Principal Investigator (Last, First, Middle): Crosby, Gregory J. ABSTRACT Delirium is the most common complication of surgery and anesthesia in older patients, afflicting 15-60% of those having non-cardiac procedures. This is a major clinical problem because nearly 40% of surgical procedures are performed on older patients and delirium is associated with serious morbidity, including accelerated decline to dementia. Still, the cause of postoperative delirium is uncertain and its neuropathogenesis is unknown. Cerebral neurodegenerative pathology characteristic of Alzheimer’s disease and related disorders is common even in cognitively normal older people, and by the time even mild symptoms develop is pronounced. We hypothesize that this preexisting burden of occult cerebral neurodegeneration accounts for enhanced vulnerability to postoperative delirium (Aim 1), augments surgery- and delirium-induced cerebral injury (Aim 2), and fuels surgery- and delirium-induced inflammation, which aggravates neural injury and increases neurodegeneration (Aim 3). We will test these hypotheses in a longitudinal prospective observational study of older surgical patients evaluated preoperatively for cognitive impairment and followed postoperatively for delirium and longer-term cognitive decline, with neurodegeneration and neural injury defined by ultrasensitive plasma biomarkers and cerebral MR imaging. This project is innovative because it addresses the key question of whether surgery and anesthesia produce delirium and persistent cognitive decline de novo or by unmasking or exacerbating a cerebral precondition and is significant because of the magnitude of the clinical problems (neurodegenerative disease, delirium), practicality of the approach (blood- based biomarkers), and potential to improve the outcomes of vulnerable older surgical patients. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page

项目负责人/主要研究者（最后一名、第一名、中间名）：克罗斯比、Gregory J. 摘要 谵妄是老年患者手术和麻醉最常见的并发症， 非心脏手术的患者。这是一个主要的临床问题，因为近40%的外科手术 手术是对老年患者进行的，谵妄与严重的发病率有关，包括 加速衰退为痴呆症尽管如此，术后谵妄的原因是不确定的， 神经发病机制尚不清楚。阿尔茨海默病的脑神经退行性病变特征 即使在认知正常的老年人中， 发展是显而易见的。我们假设这种先前存在的隐性脑神经变性负担 解释了术后谵妄的易感性增强（目标1），增加了手术和谵妄诱导的 脑损伤（目的2），并刺激手术和谵妄诱导的炎症，从而加重神经损伤 并增加神经变性（目的3）。我们将在一个纵向的前瞻性测试这些假设 对老年手术患者进行术前认知功能障碍评估和随访的观察性研究 术后谵妄和长期认知下降，伴神经变性和神经损伤 通过超灵敏的血浆生物标志物和脑MR成像来定义。这个项目是创新的，因为它 解决了手术和麻醉是否会产生谵妄和持续认知的关键问题， 通过暴露或加重大脑先决条件而从头下降，并且由于 临床问题的严重性（神经退行性疾病，谵妄），方法的实用性（血液- 基于生物标志物），并有可能改善脆弱的老年手术患者的结局。 OMB编号0925-0001/0002（修订版03/2020批准至02/28/2023）页码继续格式页码